Immune mediated or autoimmune skin diseases other than Pemphigus foliaceus are uncommon to rare in the cat.

PEMPHIGUS FOLIACEUS (PF)

PF is the most common autoimmune skin disease of cats and is generally more common in middle aged to older animals. There is no age, breed or gender predisposition. The pathogenesis of the pemphigus group of diseases involves the induction of pathogenic autoantibody to epidermal adhesion molecules. The end result is the formation of intra-epidermal, sub-corneal and follicular pustules containing individual or rafts of keratinocytes, neutrophils and in some cases eosinophils. The trigger for autoantibody production is undetermined in many cases although infectious diseases, neoplasia, ultraviolet light and drugs have been proposed. The primary intra-epidermal pustules are transient and crusting, scaling with erythema are the main skin lesions. The distribution is symmetrical and lesions predominate on the face including the nasal dorsum and planum, periocular skin and pinnae and feet especially the nail beds and pads. PF should always be considered in adult cats with paronychia. Secondary bacterial infection may occur and pruritus is variable. Progression of PF may be acute with systemic signs or it may follow a waxing and waning chronic course.

Diagnosis is by cytological examination of pustule contents (especially those from the nail fold) and identification of acantholytic keratinocytes. Histopathology with or without immunostaining supports the diagnosis. Although human PF is ANA negative, some studies have reported up to 75% of feline PF cases as positive for ANA.

First line therapy should include bactericidal antibiotics of a class that has not been administered previously. Prednisolone is the immunosuppressive drug of choice (Table1). Remission usually occurs in 10-14 days after which the dose can be gradually tailored to alternate day therapy. However, some cases remain refractory to prednisolone alone and addition of another drug such as chlorambucil is recommended. Alternatively the glucocorticoid may be changed to dexamethasone or triamcinolone. Gold salts have also been used in refractory cases of PF in cats.

Other Pemphigus syndromes

Pemphigus erythematosus has been reported in the cat. In dogs, it is now considered to be a localised photo-sensitive form of PF with predominantly facial lesions. Serum ANA, circulating desmoglein 1 auto-antibody and IgG deposition within the epithelial spaces are all reported. The problem in distinguishing this as a separate syndrome in cats is that PF is often confined to the nose, is often chronic and mild, and classically waxes and wanes. A similar clinical and pathological entity to canine Pemphigus vulgaris has been reported in the cat but the disease is so rare that extrapolations should not be made.

BULLOUS PEMPHIGOID

Bullous pemphigoid is an extremely rare disease in cats. The pathogenesis involves the binding of autoantibody to an integral component of hemidesmosomes of the basal cells, and lamina lucida of the basement membrane zone. Ulcerative lesions involve the mucocutaneous junctions and/or the skin and footpads. In cats these signs may be extremely subtle. Diagnosis is made by histopathological demonstration of sub-epidermal clefting. Electron microscopic study can demonstrate the exact level of basement membrane zone disruption and immunohistochemistry shows IgG (IgM or IgA) autoantibody and complement within the basement membrane zone. In some cases, indirect immunohistochemistry has demonstrated circulating autoantibody specific for collagen XVII. Depending on the severity of disease, treatment may include combination immunosuppressive therapy (Table 1), broad-spectrum antibiotic cover and fluid therapy.

IMMUNE-MEDIATED VASCULOPATHIES

Immune-complex vasculitis is rarely recognised clinically in cats but may occur secondary to infectious or neoplastic disease, drugs and as part of autoimmune syndromes, such as SLE. In many cases, the causative antigens are not identified. Thrombosis, haemorrhagic bullae, maculae and necrosis occur. Areas with minimal collateral circulation such as the pinnae, paws and tail tip are predisposed sites. Fever, anorexia, and clinical signs of polyarthritis and glomerulonephritis may be seen. Multiple fresh biopsies of fresh lesions may be required to demonstrate characteristic histopathological features. Immunohistochemistry may demonstrate immunoglobulin and/or complement within the blood vessel walls but is generally only of use if the lesions are less than 18 hours old. Adjunctive immunodiagnostic testing may reveal increased levels of circulating immune complexes, decreased serum complement and hypergammaglobulinaemia.

Cold agglutinin disease is a rare autoimmune haemolytic disease reported in cats and associated with cold reacting IgM erythrocyte autoantibodies. Cold agglutinins occur naturally without disease in some cats, and they have been associated with primary haemolytic anaemia and with a variety of other diseases including Haemoplasma spp. There is auto-agglutination in the peripheral vasculature at the extremities; tail tip, ear tip, pads. Microthrombi result in ischaemic skin necrosis. The Coombs test is positive and auto-agglutination at low temperature. Treatment of cutaneous immune-mediated vasculopathies in the cat involves managing the underlying cause and withdrawing any concurrent drug therapy. Any antibiotic therapy should be changed to another pharmacological group. Treatment with immunosuppressive or anti-inflammatory drugs is only indicated where infectious causes are being appropriately controlled.

CUTANEOUS AND SYSTEMIC LUPUS ERYTHEMATOSUS (CLE AND SLE) Nasal cutaneous lupus (NCL)

Most of the specific cutaneous "lupoid" diseases have been reported in dogs; the only one reported in the cat is nasal cutaneous lupus, previously referred to as discoid lupus. The immunopathogenesis of nCL has been poorly studied in dogs and cats. There is a lymphocyte-rich interface dermatitis with apoptosis and the initiating antigens have not been identified. NCL presents as a depigmenting, scaling lesion of the nasal planum followed by erosion and crusting. The mucous membrane of the lips, eyelids and footpads may be affected.

Diagnosis: Multiple biopsies should demonstrate a lichenoid dermal infiltration with a focal interface distribution. Individual apoptotic keratinocytes may be present within a viable epidermis. Immunohistochemistry is positive for immune complexes in 50% of cases and serum ANA has been negative in the few cases reported.

Therapy: In cases where ulceration is mild, prednisolone at the lowest effective dose on alternate days is usually sufficient. The use of tetracyclines and niacinamide has not been reported in the feline disease. However, Vitamin E (100-400 IU bid) may be useful and minimising UV light exposure is always recommended. Withdrawal from therapy during the winter may be possible in some geographic areas.

Systemic lupus erythematosis (SLE)

SLE is extremely rare and poorly defined in cats. Traditionally, it is a syndrome made up of dermatological and systemic immunemediated signs including interface dermatitis with positive basement membrane zone immunostaining, thrombocytopaenia, immunecomplex glomerulopathy, neutropaenia, haemolytic anaemia, polyarthritis, polymyositis and polyserositis. Cutaneous lesions are variable and include erythema, exfoliative dermatitis, and alopecia. Petechiae on the skin and mucous membranes may be present if thrombocytopaenia is part of the syndrome. Criteria for diagnosis have been adapted from the dog and include a positive antinuclear antibody test in combination with at least two of the clinical entities mentioned above. The histopathological and immunopathological features are similar to those described for cutaneous lupus. Therapy involves the use of prednisolone and chlorambucil (Table1).

FELINE PLASMA CELL PODODERMATITIS

The aetiology and pathogenesis of this disease are unknown but an immune-mediated pathogenesis has been suggested by basement membrane zone IgG deposition, positive ANA titres and the presence of intercurrent glomerulonephritis. Soft, fluctuant haemorrhagic swelling of the pads followed by ulceration occurs often with associated systemic signs of pyrexia, anorexia, and lymphadenopathy.

Diagnosis: Histopathology reveals marked dermal plasma cell infiltrate and occasional leukocytoclastic vasculitis. Response to immunosuppressive therapy is generally poor but some spontaneous resolution may be seen.

Therapy: Response to immunosuppressive therapy is variable and spontaneous resolution may be seen.

FELINE ATROPHIC AURICULAR POLYCHONDRITIS

This is postulated to be the consequence of an immune mediated attack on the aural cartilage. The histopathology is similar to human relapsing polychondritis but clinically in humans, the disease also affects joint, nasal and tracheal cartilage. The human disease is associated with the formation of a number of autoantibodies including anti-Type II collagen, anticytoplasmic and antinuclear antibody. Rheumatoid factor is often present. The immunopathogenesis in cats is unknown. Affected cats have a history of bilateral aural swelling (although the onset is usually unilateral) which is associated with pain or irritation leading to self-trauma. The medial aspect of the pinnae is erythematous. Resolution of the swelling is accompanied by deformity of the aural cartilage often with drooping of the pinnae. Fever and anorexia may accompany the acute phase of the diseases. This entity has also been associated with apparent aural cartilage weakness without clinical inflammation in Siamese cats.

Diagnosis: On histopathology there is a lympho-plasmacytic infiltrate associated with cartilage necrosis. In some cases there is a more granulomatous infiltrate which may reflect the chronicity of the lesion. Vasculitis and arteritis are part of the syndrome in humans and while fibro-vascular proliferation in aural cartilage has been described in feline cases, there are no reports of overt vasculitis. Direct immunofluorescence testing has been negative in feline cases.

Therapy: There is little available information on the use of antiinflammatory drugs in this syndrome. In one case treated in the acute phase, cartilage deformity was not prevented.

Table 1. Immunosuppressive Drugs Used For the Treatment of Feline Immune Mediated Skin Diseases